Integrins participate in various in vivo functions through the binding to adhesion molecules classified into immunoglobulin super family, sialomucin family, and the like. Integrins are composed of subunits referred to as alpha (α) and beta (β) subunits, and there have been identified sixteen α subunits and eight β subunits so far. The α4 subunit associates with the β1 or β7 subunit, and forms α4β1 and α4β7 integrins, respectively, which are hereinafter referred to as “α4 integrin” collectively.
It is known that α4 integrin is involved in various diseases through the adhesion to mucosal addressin cell adhesion molecule-1 (MAdCAM-1), vascular cell adhesion molecule-1 (VCAM-1) or connecting segment 1 (CS-1) on fibronectin. It is also known that when adhesion of α4 integrin is inhibited by an anti-α4 integrin antibody, the symptoms of allergic bronchitis, inflammatory bowel disease, rheumatoid arthritis, experimental autoimmune encephalomyelitis, and the like are alleviated.
It has been reported that there are compounds capable of inhibiting α4 integrin-mediated cell adhesion and that they are useful in treatment of diseases related to α4 integrin-mediated cell adhesion (see, WO 01/12183 and WO99/36393). However, those publications do not disclose compounds having a lower alkoxy-C1-2 alkyl group at the 4′-position of biphenylalanine nucleus, and a process for preparing the same.